Luo X N, Reddy J C, Yeyati P L, Idris A H, Hosono S, Haber D A, Licht J D, Atweh G F
Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Oncogene. 1995 Aug 17;11(4):743-50.
Wilms' tumor belongs to a small group of pediatric neoplasms that have served as paradigms of human cancers in which recessive mutations play a primary role in tumorigenesis. WT1 is a candidate tumor suppressor gene that is mutationally inactivated in a proportion of both familial and sporadic Wilms' tumors. Recent studies demonstrated that WT1 can partially suppress growth of a Wilms' tumor cell line in vitro and in vivo. We investigated the ability of WT1 to inhibit the expression of the transformed phenotype in non-Wilms' tumor cells. The expression of WT1 cDNA in ras-transformed NIH3T3 cells yielded large, flat cells that exhibited complete contact-inhibition. These morphologic changes were associated with decreased proliferation, suppression of clonogenicity in soft agar and inhibition of tumor growth in nude mice. Moreover, expression of WT1 in non-transformed NIH3T3 cells resulted in similar morphologic changes and profound resistance to transformation by an activated ras oncogene. These studies suggest that tumor inhibition by WT1 in these cells may be achieved by interference with the ras-mediated signalling pathway.
肾母细胞瘤属于一小类儿童肿瘤，它们已成为人类癌症的范例，其中隐性突变在肿瘤发生中起主要作用。WT1是一种候选肿瘤抑制基因，在一部分家族性和散发性肾母细胞瘤中发生突变失活。最近的研究表明，WT1在体外和体内均可部分抑制肾母细胞瘤细胞系的生长。我们研究了WT1抑制非肾母细胞瘤细胞中转化表型表达的能力。WT1 cDNA在ras转化的NIH3T3细胞中的表达产生了大的扁平细胞，这些细胞表现出完全的接触抑制。这些形态学变化与增殖减少、软琼脂中克隆形成能力的抑制以及裸鼠肿瘤生长的抑制有关。此外，WT1在未转化的NIH3T3细胞中的表达导致了类似的形态学变化以及对活化的ras癌基因转化的深度抗性。这些研究表明，WT1在这些细胞中的肿瘤抑制作用可能是通过干扰ras介导的信号通路实现的。
